Bombesin, a tetradecapeptide amide first isolated from the skin of the frog Bombina bombina, is a potent mitogen for mouse Swiss 3T3 fibroblast cells. It also stimulates secretion for guinea pig pancreatic acini. Bombesin-like peptides are produced and secreted by human small cell lung cancer cells and exogenously added bombesin-like peptides can stimulate the growth of human SCLC cells in vitro. Two examples of bombesin-like peptides are gastrin releasing peptide (GRP) and neuromedin B (NMB).
GRP is a 27 amino acid peptide amide and was first isolated from the porcine gut. The C-terminal amino acid sequence of GRP is almost identical to that of bombesin. NMB, on the other hand, is a decapeptide amide, the structure of which is almost identical to the last ten amino acids in the C-terminal region of GRP. Both GRP and NMB share high amino acid sequence homology with bombesin and indeed possess bombesin-like properties. Other bombesin-like peptides include litorin and neuromedin C (NMC).
Recent structure-function and DNA cloning studies demonstrate that at least two classes of receptors mediate the action of bombesin-like peptides. One class, the GRP preferring subtype (GRP receptor), has a high affinity for GRP and a low affinity for NMB, whereas the other class, the NMB-preferring subtype (NMB receptor), has a high affinity for NMB and lower affinity for GRP. Both classes of receptors are widely present both in the central nervous system and in the gastrointestinal tract. A third receptor class, the BRS-3 receptor, has recently been found in both rat testes and pregnant uteruses. Unlike the GRP and NMB receptors, none of the presently known bombesin-like peptide binds with high affinity (K.sub.d &lt;25 nM) to the BRS-3 receptor.